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Biometals ; 17(6): 635-45, 2004 Dec.
Article in English | MEDLINE | ID: mdl-15689107

ABSTRACT

The Cu(II) and Ag(I) complexes, [Cu(phendio)3](ClO4)2 x 4H2O and [Ag(phendio)2]ClO4 (phendio = 1,10-phenanthroline-5,6-dione), are prepared in good yield by reacting phendio with the appropriate metal perchlorate salt. The X-ray crystal structure of the Ag(I) complex shows it to have a pseudo tetrahedral structure. 'Metal-free' phendio and the Cu(II) and Ag(I) phendio complexes strongly inhibit the growth of the fungal pathogen Candida albicans, and are more active than their 1,10-phenanthroline analogues. The simple Ag(I) salts, AgCH3CO2, AgNO3 and AgClO4 x H2O display superior anti-fungal properties compared to analogous simple Cu(II) and Mn(II) salts, suggesting that the nature of the metal ion strongly influences activity. Exposing C. albicans to 'metal-free' phendio, simple Ag(I) salts and [Ag(phendio)2]ClO4 causes extensive, non-specific DNA cleavage. 'Metal-free' phendio and [Ag(phendio)2]ClO4 induce gross distortions in fungal cell morphology and there is evidence for disruption of cell division. Both drugs also exhibit high anti-cancer activity when tested against cultured mammalian cells.


Subject(s)
Copper/pharmacology , Perchlorates/pharmacology , Phenanthrolines/chemical synthesis , Phenanthrolines/pharmacology , Animals , Antineoplastic Agents/pharmacology , Candida albicans/metabolism , Cell Line, Tumor , Crystallography, X-Ray , Cytokinesis , DNA, Fungal/metabolism , Fungal Proteins/metabolism , Humans , Metals/chemistry , Microscopy, Electron , Models, Chemical , Perchlorates/chemical synthesis , Protein Conformation , X-Rays
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